History of Plague - Plague Through the Ages

Plague is a zoonotic disease caused by infection with Yersinia pestis. In nature, plague cycles in its enzootic and epizootic foci, circulating between small mammals and fleas without human involvement.1, 2 Humans come into contact with Y. pestis by being bitten by a rodent flea that is carrying the plague bacterium or by handling an infected animal. Plague can present three clinical features: bubonic plague (characterized by development of an acute regional lymphadenopathy, or bubo, is the most common clinical form of disease, it has 50% mortality rate untreated), septicemic plague (occurs when Y. pestis invades and continues to multiply in the bloodstream, can occur secondarily to bubonic plague, it has 50% mortality rate untreated), and pneumonic plague (most dangerous and fatal form of the disease, it can result from inhalation of respiratory droplets from a human or animal that has plague pneumonia, it has close to a 100% mortality rate untreated).1

Plague is an ancient and well documented disease; several historical references describe epidemics that are symptomatic of infection with Y. pestis. The biblical book of I Samuel describes how the Philistines were punished for stealing the Ark of the Covenant from the Israelites &ldquo;with an outbreak of tumors in the groin.&rdquo; Also known as the Plague of Ashdod, the plague spread with the movement of the Philistines to Ashdod, Gath, and finally Ekron during the second half of the eleventh century BC.1, 3 The Libyan plague of the 1st century AD is one of the earliest identifiable instances of bubonic plague. Dioscorides and Posidonius, two physicians from Alexandria, chronicled a disease characterized by fever, intense pain, delirium, and non-suppurating buboes.3

Plague reached pandemic proportions in 541 AD, in what is known as the First Pandemic or Justinian's Plague, which raged until 544 AD. This pandemic originated either in Ethiopia, moving through Egypt, or in the Central Asian steppes, where it then traveled along the caravan trading routes. The movement of troops during the campaigns of Justinian provided another source for the plague expansion. The disease spread from Asia Minor to Africa and to the Mediterranean littoral.4 On its second year, the plague reached Constantinople, the capital of the Byzantine Empire, where it killed about 300,000 people within that year. John of Ephesus, Evagrius Scholasticus, and Procopius gave detailed descriptions of the symptoms: “They had a sudden fever&hellip;but [sic] on the same day in some cases, in others on the following day, and in the rest not many days later, a bubonic swelling developed; and this took place not only &hellip; "below the abdomen," but also inside the armpit, and in some cases also beside the ears, and at different points on the thighs.” It is estimated that as many as 100 million Europeans perished.1, 5

Repeated, smaller epidemics followed, including the Roman Plague of 590 and the Frankish Plagues of the Sixth Century, during which several scholars give accounts of plague-like symptoms.3

The First Plague Pandemic, in spite of its staggering human toll, was not as well known and dreaded as the Second Pandemic of the 1347, which became known as the Black Death, the Great Mortality, and the Great Pestilence. It originated in Asia, most likely in China, in the early 1340s, carried by rats and fleas along the Silk Road caravan routes. From China it spread to India, Egypt, and all of Asia Minor. By the time it reached Constantinople, it had already killed an estimated 25 million Asians. From there the plague quickly spread through maritime routes to Genoa, Marseilles, and other Mediterranean ports. By 1350, the Black Death had spread throughout Europe (including Iceland and Greenland).1, 5

Based on numerous descriptions of the symptoms of plague victims, bubonic plague was the predominant clinical manifestation of the disease in Europe. However, pneumonic plague appeared to be prevalent in epidemics in Alexandria, Damascus, and other cities in the Middle East. In 1348, over 7,000 people in Cairo were dying daily from both pneumonic and septicemic plague.3

The estimated population of Europe in 1347 was 75 million; by 1352, the population had declined to 50 million.4, 6 The Plague of Florence or the Black Vomit (1347-48), chronicled in Boccaccio&rsquo;s The Decameron, resulted in the death of 40% to 75% of the city&rsquo;s population. The Great Plague of England 1348-50 killed as much as 40% of the population of British Isles.3

In his introduction to TheDecameron, Boccaccio gives a detailed account of the devastating consequences of the Black Death:

&ldquo;The condition of the lower, and, perhaps, in great measure of the middle ranks, of the people shewed &hellip; more deplorable; for, deluded by hope or constrained by poverty, they stayed in their quarters, in their houses where they sickened by thousands a day, and, being without service or help of any kind, were, so to speak, irredeemably devoted to the death which overtook them.&rdquo;

Boccaccio also makes reference to the attempts of health officials in Florence to stave off the disease by taking sanitation and quarantine measures. Historians often mention the unsanitary conditions of medieval cities that were conducive to the spread of the plague. As the plague raged through Europe, it affected the general understanding of public health. Beginning in Italy in the 1350s there were new initiatives aimed at raising the level of public sanitation. After the plague of 1348, King Edward III issued an order to the Lord Mayor of London to clean up the streets. By the sixteenth century the European medical community, even if it had not yet identified the etiologic agent or vectors of the disease, had accepted contagion as the likely cause of the plague. Cities such as Venice and Milan went on to establish advanced public health measures.

At the time, lay and religious authorities sought an explanation for the plague. The pestilence was attributed to many things, from &ldquo;hot and humid southerly winds&rdquo; to putrid decomposition of diseased bodies, to women with leprosy. The church&rsquo;s popularity waned due in part to the inability of religious authorities to abate the pestilence.6 People sought comfort and protection by venerating new saints, including Saint Sebastian, Saint Roch, and Saint Lorenzo. Viewing the plague as a punishment from God, some sought to abate God&rsquo;s anger through self-inflicted whipping, or flagellation. The Brotherhood of the Flagellants, a movement said to number up to 800,000, reached its peak of popularity during the Black Death. Fear and superstition lead to the persecution of Jews throughout Europe. In May 1348, Jewish communities were accused of poisoning the wells in France and were completely exterminated. In January 1349, all Jews were locked inside wooden buildings and burned alive in Basel, Switzerland.

In spite of the death toll, Europe flourished economically because depopulation allowed wealth and improved standard of living for more people. The economy underwent abrupt and extreme inflation. Labor shortages lead to higher wages and wider selection of jobs as well as to higher prices for crafted items. The Ordinance of Laborers of 1349 in England was one of several futile attempts to control prices. To many historians, the plague marked the end of the Middle Ages. Viewed as a new way of life, it contributed to the end of the feudal system. The new philosophical and scientific outlook of the time paved the way for the Renaissance.

The Second Pandemic persisted until the early 17th century. Chronic depopulation continued because of cyclical epidemics. In England, for example, epidemics would continue in 2- to 5-year cycles from 1361 to 1480. Each of these epidemics is reported to have had a 10% to 15% mortality rate. Epidemics in other countries continued to have a catastrophic toll. During the Venetian plague of 1577, half of the city&rsquo;s 180,000 inhabitants contracted the disease and close to 50,000 died as a result. The Prussian Plague of 1602 killed 36% of the 49,000 inhabitants of the port city of Danzig and was the first of three major outbreaks that the city would see within a hundred years. In 1634, an outbreak of bubonic plague killed 15,000 Munich residents.3 The frightened population of nearby Oberammergau prayed to be spared and vowed to do something in which everyone would participate: a Passion Play. They would present the story of Christ to the world every 10 years in perpetuity if the Lord would remove the plague from their people. The town was spared and the play continues to this day.

The Third Pandemic or Modern Pandemic of 1894-1959, swept across Asia in the 1890s, from Canton (probably though military activity) to Hong Kong and then Bombay, killing about one million people in India in 1903.1, 3 Subsequently, the plague invaded Java, Japan, Asia Minor, South Africa, the shores of North and South America, Portugal, Austria, and parts of Russia. There were an estimated 26 million plague cases and more than 12 million deaths, the vast majority in India.

Plague had circled the globe quickly and, by 1910, established stable enzootic foci on all inhabited continents other than Australia. Plague reached the United States west coast in 1900. In the summer of 1899, the SS Nippon Maru, sailing from Hong Kong to San Francisco, had two cases of plague on board. Despite this scare, there was no immediate outbreak of disease. It is speculated that rats from the ship probably had something to do with the epidemic that hit San Francisco nine months later. The same ship is believed to be responsible for the Hawaiian Plague of 1899-1900. The San Francisco Plague of 1900-04 resulted in 122 cases and 121 fatalities; hardest hit was San Francisco&rsquo;s Chinatown. The San Francisco Plague of 1907-09 was to some extent the result of the unsanitary, cramped conditions existing in some neighborhoods destroyed by the earthquake of 1906. Unlike the epidemic of 1900, public health measures were quickly implemented, including a rat control campaign similar to one used successfully in other port cities by the U.S. Public Health Service.3

The mortality rate and dissemination of plague outbreaks during this pandemic were significantly reduced compared to previous pandemics.1, 4 This is largely due to key scientific advancements and improved public health measures occurring at the turn of the century. After 1920, the spread of plague was largely halted by international regulations that mandated control of rats in harbors and inspection of ships. By 1950, plague outbreaks around the world had become isolated, sporadic, and manageable with modern techniques of surveillance, flea and rat control, and the use of antibiotics for the treatment of patients.

During the Hong Kong Plague of 1894, Alexandre Yersin, a Swiss Pasteurian, and Shibasaburo Kitasato, from Japan, isolated almost simultaneously the plague bacillus. Yersin prepared a serum to combat the disease. Shortly after this, Masanori Ogata, of the Hygiene Institute in Tokyo, proved that fleas taken from infected rats contain plague bacilli. In 1897, Paul-Louis Simond proved that fleas transmitted plague. In 1897, Waldemar Haffkine, a Russian bacteriologist working in Bombay,developed a preventive vaccine using killed broth cultures of the plague bacillus.1

Plague in the modern era

Major outbreaks occurred in Indonesia, Africa, South America, and Vietnam in the 1960s and 1970s. The Vietnamese Plagues of the 1960s were a major concern for the United States military during the Vietnam War. However, because of sanitation measures, vaccination, and the use of antibiotics, only eight US troops were infected. The local population did not fare as well, it is estimated that between 100,000 and 250,000 plague cases occurred in Vietnam between 1964 and 1974. Plague continues to be endemic and sporadically epidemic in Vietnam, 63% of cases in Asia reported to the World Health Organization from 1984 to 1999 occurred in this country.1, 2

During the 1960s, US Army officers, Lieutenant Colonel Dan C. Cavanaugh and Lieutenant Colonel John D. Marshall, studied plague ecology, related plague epidemics to weather as a function of flea physiology, developed serologic tests for plague infection, and developed the data to demonstrate the efficacy of a whole-cell killed plague vaccine.1

Plague has practically disappeared from cities and now occurs mostly in rural and semirural areas, where it is maintained in wild rodents. The World Health Organization (WHO) reported 18,739 cases, including 1853 deaths, of human plague between 1980 and 1994 from 24 countries. WHO continues to report 1,000 to 3,000 cases of plague globally every year.7 In the United States, the last outbreaks of urban plague occurred in Los Angeles in 1924 and 1925, and human cases since then have resulted from zoonotic exposures in rural areas of western states (New Mexico, Arizona, Colorado, Utah, and California), an average of 10 to 20 persons each year.8 Enzootic foci continue to occur in North America (western United States, southwestern Canada, northern Mexico), South America (including Peru, Venezuela, Ecuador, Brazil), Africa (including South Africa, Lesotho, Madagascar, Namibia), extreme southeastern Europe, and Asia (from the desert and steppe regions of the Caucasus to northeast China).2 Plague, because of its pandemic history, remains one of three quarantinable diseases subject to international health regulations (the other two being cholera and yellow fever).

The plague as a biological weapon

In 1346, the plague came to Kaffa, a Genoese-controlled port city located on the Black Sea. The Tartar forces of Kipchak Khan Janibeg, backed by Venetian forces - competitors of the Genoese - had laid siege to Kaffa in hopes of removing Genoa's dominance of east-west trade. But then, in 1347, Janibeg's army was overcome by the plague. Janibeg had no choice but to call off his siege, but not until he catapulted the plague-infested corpses of his dead men into the city.1 Plague soon broke out in Kaffa. Modern epidemiologists speculate that it is unlikely that the plague was caused solely by this attack, but was probably imported by sylvatic and urban rodents and their fleas, and exacerbated by the deteriorating sanitary conditions caused by the siege.9 Hoping to escape the quickly spreading disease, four Genoese ships departed from Kaffa to Constantinople, Genoa, and Venice, likely carrying infected refugees and rodents. Janibeg&rsquo;s tactic was replicated as late as the early 18th century, when Russian troops fighting Sweden resorted to catapulting plagued bodies over the city walls of Reval.

During World War II, the Japanese army established a secret biological warfare research unit, known as Unit 731, in Pingfan, Manchuria. In 1940 and 1941, Japanese aircrafts spread cotton and rice husks mixed with plague-infected fleas over Changde and Ningbo, in central China. Over 100 people reportedly died from plague in Ningbo as a result. Although the Chinese National Health Administration attributes wartime plague epidemics on these attacks by the Japanese of Unit 731, conditions in China during the war precluded rigorous epidemiological and bacteriological data collection.1, 2, 8

During the decades following the ratification of the Biological Weapons Convention of 1972, the Soviet Union, a signatory to the treaty, continued participating in covert biological research programs. Kantjan Alibekov, First Deputy Director of the Soviet biological weapons program Biopreparat from 1988-1992, defected in 1992. He claims that 20 tons of plague were manufactured and stockpiled at the Kirov facility.

The Working Group on Civilian Biodefense identified in May of 2000 a limited number of agents that, if used as weapons, could cause disease and death in sufficient numbers to cripple a city or region. Yersinia pestis is included among these pathogens because of the capacity for its mass production and aerosol dissemination, high fatality rate of pneumonic plague, and potential for secondary spread of cases during an epidemic.9

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